Permeability of Lung Epithelium to

Although there are two known immunoglobulin transporters, the poly Ig receptor for secretory IgA (14) and the FcRn receptor for IgG (15,16), they most likely do not play a major role in E25 transport across lung epithelium as evidenced by the data described below. 

In Vitro Studies Airway and Alveolar Cell Culture Models 

We used in vitro models of lung epithelial cell lines or primary cells to determine E25 permeability. Two different cell types were used to mimic the airway and alveolar epithelium of the lung to study transport. Calu-3, a human cell line derived from an airway carcinoma, when grown at an air/liquid interface, differentiate to form a secretory airway epithelium (17). Rat primary epithelial cells isolated as described by Cheek et al. (18) form a tight barrier similar in structure and function to the alveolar surface. Both cell types when grown to confluence form tight junctions and differentiate and polarize so that the apical or air surface has different characteristics than the basolateral or blood side. The typical transepithelial resistance observed was 350 or 1000 ohms-cm for Calu-3 cells or primary rat alveolar cells, respectively. Once an acceptable resistance was achieved, E25 (2 mg/mL) was placed in either the apical or the basolateral chamber. Cell monolayers were incubated at 37°C for up to 3 hours and ELISA measured the amount of E25 that translocated the epithelial layer and appeared in the receiver well. The apparent permeability (Papp) of the epithelium for E25 was calculated as  

E25 had similar permeability in both cell types and 10-fold higher permeability in the basolateral to apical direction than in the apical to basolateral direction (see Table 1). In either direction, permeability across airway or alveolar epithelium to the antibody (E25) was low. Similar transport rates were obtained by Kim and Crandall (19) for an IgG antibody in rat alveolar epithelial cells, although directional preferences for transport were the opposite of those observed in Table 1. 

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